Plaza-Oliver María, Cano Emilio L, Arroyo-Jimenez María Mar, Gámez Matías, Lozano-López María Victoria, Santander-Ortega Manuel J
Cellular Neurobiology and Molecular Chemistry of the Central Nervous System Group, Faculty of Pharmacy, University of Castilla-La Mancha (UCLM), 02071 Albacete, Spain.
Regional Centre of Biomedical Research (CRIB), University of Castilla-La Mancha (UCLM), 02008 Albacete, Spain.
Pharmaceutics. 2021 Mar 10;13(3):370. doi: 10.3390/pharmaceutics13030370.
The success on the design of new oral nanocarriers greatly depends on the identification of the best physicochemical properties that would allow their diffusion across the mucus layer that protects the intestinal epithelium. In this context, particle tracking (PT) has arisen in the pharmaceutical field as an excellent tool to evaluate the diffusion of individual particles across the intestinal mucus. In PT, the trajectories of individual particles are characterized by the mean square displacement (), which is used to calculate the coefficient of diffusion () and the anomalous diffusion parameter () as MSD=4Dτα. Unfortunately, there is no stablished criteria to evaluate the goodness-of-fit of the experimental data to the mathematical model. This work shows that the commonly used parameter may lead to an overestimation of the diffusion capacity of oral nanocarriers. We propose a screening approach based on a combination of with further statistical parameters. We have analyzed the effect of this approach to study the intestinal mucodiffusion of lipid oral nanocarriers, compared to the conventional screening approach. Last, we have developed software able to perform the whole PT analysis in a time-saving, user-friendly, and rational fashion.
新型口服纳米载体设计的成功很大程度上取决于能否确定最佳的物理化学性质，这些性质可使纳米载体穿过保护肠上皮的黏液层。在此背景下，粒子追踪（PT）在制药领域应运而生，成为评估单个粒子在肠道黏液中扩散的出色工具。在粒子追踪中，单个粒子的轨迹通过均方位移（MSD）来表征，均方位移用于计算扩散系数（D）和反常扩散参数（α），公式为MSD = 4Dτα。遗憾的是，目前尚无既定标准来评估实验数据与数学模型的拟合优度。这项工作表明，常用的α参数可能会高估口服纳米载体的扩散能力。我们提出了一种基于α与其他统计参数相结合的筛选方法。与传统筛选方法相比，我们分析了该方法在研究脂质口服纳米载体肠道黏液扩散方面的效果。最后，我们开发了一款软件，能够以省时、用户友好且合理的方式进行完整的粒子追踪分析。
